Ricerc@Sapienza

The natural history and pathophysiology of diverticular disease (DD) is still under definition and efforts continued to identify risk factors and to establish relative preventive strategies. The increasing socioeconomic burden of DD has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Efforts have been made to identify risk factors to establish relative preventive strategies and to achieve more standardized treatment approaches. Recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals.
A multifactorial pathogenesis has been hypothesized for uncomplicated and complicated DD with likely different interconnections between luminal and extra-luminal colonic microenvironments that converge on the cornerstone pathophysiological mechanism of diverticula formation and complications that lies in a loss of colonic compliance with increased intraluminal pressure in colonic haustra related to a smooth muscle hypertrophy and remodeling contributing to wall fibrosis. The actual therapeutic strategies aimed to modulate luminal gut microbiota, as rifaximin or probiotics, or aimed to reduce mucosal inflammation, as mesalazine, present a relative poor efficacy both for the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). Extra-luminal factors, namely muscle layers and visceral fat, have been studied in less details even if they appear to represent the targets of AD risk and protective factors and to be influenced by age and gender.
In the context of risk stratification, the aim of the present project is to identify possible age- and gender-dependent alterations, mainly focused on extra-luminal factors, that could contribute to DD and discriminate different pathogenic phenotypes that characterize more aggressive and complicated DD.